Comment on “Effectiveness of Antenatal Intravenous Immunoglobulin Treatment in Recurrent Fetal and Neonatal Alloimmune Thrombocytopenia”

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare but serious condition that occurs when maternal antibodies cross the placenta and target fetal platelet antigens inherited from the father. This immune response can lead to severe fetal thrombocytopenia and complications ranging from mild bleeding to intracranial hemorrhage. Diagnosis typically occurs after birth due to a lack of standardized screening, and recurrence rates in subsequent pregnancies are high. Current management involves antenatal intravenous immunoglobulin (IVIG) therapy, sometimes supplemented with steroids, but evidence for its effectiveness is limited. This study aimed to evaluate the effectiveness of IVIG in recurrent FNAIT and to assess whether treatment response and associated clinical factors can predict outcomes in subsequent pregnancies. This retrospective cohort study included pregnant women diagnosed with FNAIT and managed at a single tertiary center in Israel between 1992 and 2024. Clinical data were obtained from electronic medical records, including maternal, obstetric, delivery, and neonatal characteristics. Diagnosis of FNAIT was confirmed through maternal-fetal platelet antigen incompatibility and maternal antibody testing. Subsequent pregnancies were presumed to be affected if the father was homozygous for the sensitized antigen, while FNAIT status in cases of a heterozygous father was determined by second-trimester amniocentesis. Management included weekly IVIG therapy starting mid-pregnancy, with dose adjustments based on prior response, and monitored with serial neurosonography. The outcomes of interest were neonatal platelet count and presence of intracranial hemorrhage, with a good treatment response defined as the absence of hemorrhage and platelet count ≥50,000/μL at birth. Statistical analyses compared outcomes across pregnancies and between responders and nonresponders. A total of 91 women (225 pregnancies) with FNAIT were identified, of which 121 (53.8%) pregnancies received IVIG treatment. Untreated pregnancies often showed severe thrombocytopenia, whereas IVIG-treated pregnancies had improved outcomes, with no cases of intracranial hemorrhage and fewer neonates with platelet counts <50,000/μL (17.4% vs. 61.5%). Overall, 82.6% of treated pregnancies achieved a good response. Poor response was associated with HPA-1a incompatibility (95.2% vs. 60.0%), while HPA-5 was linked to better outcomes (29.0% vs. 4.8%). Across consecutive pregnancies, response to treatment was generally consistent, with some individual outliers. Despite adjustments in treatment timing and dose based on responsiveness to IVIG, disease severity and progression varied between cases. Adverse effects of IVIG were generally mild, though 11.6% of cases resulted in severe events that required discontinuation of medication or early delivery. This study found that response to IVIG in one FNAIT-affected pregnancy does not reliably predict outcomes in subsequent pregnancies. Although IVIG remains the standard therapy and is generally effective in preventing severe thrombocytopenia and intracranial hemorrhage, ~20% of cases do not respond, particularly those associated with HPA-1a incompatibility. This variability may reflect differences in disease severity or possible treatment tolerance, though no clear predictive factors were identified. These findings suggest limitations in current management, potential overtreatment in lower-risk cases, and the need for individualized approaches and further research to better predict treatment response in recurrent FNAIT. (Summarized from Zloto K, Cohen S, Batsry L, et al. Effectiveness of antenatal intravenous immunoglobulin treatment in recurrent fetal and neonatal alloimmune thrombocytopenia. Ultrasound Obstet Gynecol . 2025;66:773–780. doi:10.1002/uog.70105).